The proposal outlines experiments to study the pathogenesis altered lung development in perinatal rats derived from teratogen-treated pregnancies. A teratogenic regimen will be established during the fetal stages of rat development. The fetal rat lung is known to undergo extensive histologic and cytologic development during the last third of pregnancy. The time course of these normal sequences has been established in our animals. The ontogeny and occurrence of specific development horizons in our strain is largely similar to reports published on other strains. Specific developmental end points are present in the histologic and cytologic development of rat lung. The first objective of the proposed research is to study further, by routine techniques the pathogenesis of the histologic abnormalities present at term. The second objective is to examine the postnatal respiratory function of the pups prior to their death. The third goal is application of additional staining and evaluative techniques for a detailed examination of specific components of the neonatal lung adversely affected by the teratogen as well as those mainfesting no effect. Normal and experimentally-altered lung histologic and cytologic development will be studied in timed rat pregnancies. Specific histochemical and appropriate enzyme digestion methods are proposed for evaluation of specific cell types and tissues. During development the time course and localization patterns of specific connective tissue fiber formation, blood vessel development and location, intra-septal cell types, and epithelial differentiation will be studied. These examinations will be made in standard paraffin-embeded sections and in plastic-embeded sections with both light and transmission electron microscopy. Functional capabilities of teratogen-treated lungs will be determined and compared with those of normal neonates. These functional tests will be used to measure functional manifestations of those specific histologic and cytologic components of lung found to be altered in preliminary experiments of the past year. Routine examinations will be made of placental and other fetal organs during the pre and neonatal periods.